Neonatal NK cells target the mouse duct epithelium via Nkg2d and drive tissue-specific injury in experimental biliary atresia.

ABSTRACT: Biliary atresia is a neonatal obstructive cholangiopathy that progresses to end-stage liver disease. Although the etiology is unknown, a neonatal adaptive immune signature has been mechanistically linked to obstruction of the extrahepatic bile ducts. Here, we investigated the role of the innate immune response in the pathogenesis of biliary atresia. Analysis of livers of infants at diagnosis revealed that NK cells populate the vicinity of intrahepatic bile ducts and overexpress several genes involved in cytotoxicity. Using a model of rotavirus-induced biliary atresia in newborn mice, we found that activated NK cells also populated murine livers and were the most abundant cells in extrahepatic bile ducts at the time of obstruction. Rotavirus-primed hepatic NK cells lysed cholangiocytes in a

SUBMITTER: Shivakumar P 

PROVIDER: S-EPMC2719928 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature